Studies were carried out to determine the possible roles of the polyamines, cyclic nucleotides, icosanoid products, and protein kinase C in the prolactin regulation of amino acid transport in cultured mammary gland explants derived from 12-14 day pregnant mice. Elevated cyclic AMP concentrations impaired the PRL stimulation of AIB transport. DBcAMP as well as the phosphodiesterase inhibitors theophylline and methyl isobutylxanthine, when added to the cultures, attenuated or abolished the PRL responses. 8-Bromo cyclic GMP elicited a modest stimulation of AIB transport. Ongoing polyamine synthesis appears to be necessary for PRL to effect a stimulation of AIB transport since methylglyoxal bis(guanyl hydrazone), an inhibitor of S-adenosyl methionine decarboxylase, abolishes the PRL response; specificity of this effect was established by its reversal with the addition of spermidine to the culture medium. Ongoing icosanoid product synthesis also appears to be required for the PRL stimulation of AIB transport since indomethacin abolishes the PRL response. Finally, the inhibition of the PRL response by the protein kinase C inhibitor H-7 suggests that the activation of kinase C activity may also be involved in the PRL stimulation of AIB transport.
